11/2009 - Prof. Dr. Eberhard Straube/ PD Dr. Sigrun Eick
Influence of Porphyromonas gingivalis on kallikrein-kinin system

Abstract
Proinflammatory mediators formed by the kallikrein-kinin system, e.g. bradykin, can stimulate bone resorption and maintain inflammation in periodontitis. So it was shown that IL-1 and TNFα, two important cytokines in periodontitis enhance kinin B1 and B2 receptor expression. Despite only limited knowledge a direct influence of Porphyromonas gingivalis, a major periodontopathogenic species, might not be neglected. Bradykinin is efficiently stimulated by proteases of P. gingivalis (gingipains), mainly Rgp. On the other hand yet unpublished data from Jan Potempa suggest that bradykinin may be converted into desArg9-bradykinin (desArg9-BK, bradykinin without C-terminal arginine) by an arginine-specific carboxypeptidase of P. gingivalis (Arg-CPD). Bradykinin signals through kinin B2 receptor (B2R), whereas desArg9-BK is very potent agonist of B1 receptor (B1R).
The purpose of the project planned in collaboration with Jan Potempa (Jagiellonian University of Krakow, Poland) and Heiko Herwald (Lund University, Lund, Sweden) is to characterize in vitro the interaction of P. gingivalis carboxypeptidase and Rgp with bradykinin showing the reconstitution of desArg9-BK. This in vitro system should contain first human plasma as well as Rgp and Arg-CPD. Further instead of plasma high molecular weight kininogen, prekallikrein as single components of the kallikrein-kinin system are tested. The results of the Arg-CPD and Rgp have to be confirmed by P. gingivalis wild type strain, Arg-CPD null mutant and P. gingivalis Rgp-null mutant and clinical isolates of P. gingivalis. Furthermore the in vitro study should demonstrate the switch from B2R ligand which gives rise to a transient inflammatory response to B1R stimulation which promotes a sustained response by P. gingivalis.
 

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